蛋白磷酸酶1而非蛋白磷酸酶2A可使DNA损伤应激诱导的p53第15位丝氨酸去磷酸化。

Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA-damaging stress-induced phospho-serine 15 of p53.

作者信息

Haneda Masataka, Kojima Eiji, Nishikimi Akihiko, Hasegawa Tadao, Nakashima Izumi, Isobe Ken-ichi

机构信息

Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-cho, Obu, Aichi 474-8522, Japan.

出版信息

FEBS Lett. 2004 Jun 4;567(2-3):171-4. doi: 10.1016/j.febslet.2004.04.066.

DOI:10.1016/j.febslet.2004.04.066

PMID:15178317

Abstract

Okadaic acid (OA) is a protein phosphatase (PP) inhibitor and induces hyperphosphorylation of p53. We investigated whether the inhibition of PP1 by OA promotes the phosphorylation of the serine 15 of p53. In vitro dephosphorylation assay showed that PP1 dephosphorylated ultraviolet C (UVC)-induced phospho-ser15 of p53, and that OA treatment inhibited it. One of the PP1 regulators, growth arrest and DNA damage 34 (GADD34), disturbed PP1 binding with p53, interfered with the dephosphorylation of p53 and increased the amount of phospho-p53 after UVC-treatment. This report provides the first evidence that PP1, but not PP2A, dephosphorylates phospho-serine 15 of p53.

摘要

冈田酸（OA）是一种蛋白磷酸酶（PP）抑制剂，可诱导p53的过度磷酸化。我们研究了OA对PP1的抑制是否会促进p53丝氨酸15位点的磷酸化。体外去磷酸化试验表明，PP1可使紫外线C（UVC）诱导的p53磷酸化丝氨酸15去磷酸化，而OA处理可抑制这一过程。PP1调节因子之一，生长停滞和DNA损伤诱导蛋白34（GADD34），干扰PP1与p53的结合，干扰p53的去磷酸化，并增加UVC处理后磷酸化p53的量。本报告首次证明PP1而非PP2A可使p53的磷酸化丝氨酸15去磷酸化。